With aging, female rats exhibit a gradual cessation of regular ovulatory function and a decline in fertility (% of females with successful pregnancy) and fecundity (litter size). At present, it is unknown whether increased reproductive failures at old age is due to a loss of regular ovulatory function, ovarian steroid deficiency inadequate for implantation and pregnancy maintenance, reduced uterine responsiveness to ovarian steroid during gestation, increased incidence of implantation failures. and/or decreased ovulation rate. This proposal outlines sytematic approaches to study the biology and endocrinology of pregnancy with aging. In virgin rats of young, middle, and old age, studies will be performed to compared the numbers of ova shed per ovulation and morphologically normal and abnormal blastocytes recovered, to compare the number of implantations observed by laparotomy and live pups delivered at term of first pregnancy, and to delineate the patterns of pituitary prolectin and ovarian estradiol, testosterone, and progestin secretion during pregnancy. In these same groups of aging rats, repetitive pregnancy studies will be carried out longitudinally to reveal the chronological changes in the biology and endocrinology of pregnancy with aging in the same individual females. The results from these will definiterly determine whether aging affects ovulation rate, pre- and post-implantation failures, litter size, and/or prolactin and steroid hormone secretion during pregnancy, and indicate possible relationship between hormone alterations and implantation failures. The longitudinal studies also will reveal whether previous gestation(s) influences the subsequent pregnancy performance in aging multiparous females. Since many aging rats change from a regular cyclic to an irregular cyclic state, and the onset of irregular cyclicity is associated with major alterations in LH and ovarian steroid secretion, our studies will examine the efficacy of pregnancy performance by irregular cyclic aging females. To determine if decreased uterine responsibeness to steroids contributes to increased implantation failures at old age, pregnant aging females will be ovariectomized and treated with estradiol and progesterone and the effect on implantations will be evaluated. The overall objective of this proposal is to test whether ovarian steroid deficiency in aged pregnant females results in increased implantation failures, thereby decreasing the fertility and fecundity. These findings, if significant, will be of great benefit to our clinical management of older women desiring child birth.